Thursday, February 27, 2014

Research Update: Laminitis and Lameness Project Funding Announced by Grayson-Jockey Club Research Foundation

Grayson-Jockey Club Research Foundation’s board of directors has announced a slate of 19 research projects which the Foundation will fund for a total of $1,003,580 in 2014. The list includes eleven new projects and five which are in their second year, as well as three Storm Cat Career Development Awards.

Funding decisions for research grants are made by the board after input from a 32-person Research Advisory Committee, which is composed of researchers and veterinarians representing various specialties. Grayson-Jockey Club Research Foundation received 59 proposals for research for the 2014 funding cycle.

The breakdown of the 11 new regular projects being funded is infectious disease, five; musculoskeletal soundness, three; laminitis, two; respiratory (non-infectious) disease, one. A list of laminitis and lameness projects is published here.The allotment brings the Foundation’s total impact since 1983 to $20.9 million; the organization has funded 310 projects at 41 universities.

Laminitis Research

Equine laminitis continues to be a devastating complication to multiple equine diseases. Laminitis is reported to affect 2–7% of horses annually. Due to frequency and severity of the disease, it has been listed as the number one priority for equine research by the members of the American Association of Equine Practitioners (AAEP), and as a priority for the Grayson-Jockey Club Research Foundation, USDA, etc.

From research performed in the past decade it has emerged that there are three distinct major forms of laminitis. One of them is supporting-limb laminitis. Although it has never been proven, supporting limb laminitis is suspected to occur as a result of reduced blood supply to the connection between hoof and bone (the lamellar tissue). It is proposed that horses rely upon regular loading and unloading of the foot in order to move blood (containing nutrients and oxygen) through it. Our research groups (Queensland, U of Penn, and Ohio State), supported by the Grayson-Jockey Club Research Foundation, now have strong preliminary data that supports this theory.

This next step will utilize a protocol that combines real–time monitoring of lamellar tissue blood flow and energy balance with a suitable and humane model of preferential weight bearing on one limb. We seek to confirm the cause of supporting limb laminitis and to test potential therapeutic interventions. It is anticipated that the results of this study will directly guide the design of devices and/or protocols that can be used in the clinical setting to prevent supporting limb laminitis.

An effective preventative strategy would be a significant step forward for the welfare of horses and for the horse industry.

Sepsis–related laminitis (SRL) is a common type of laminitis which occurs in animals experiencing far large breadth of diseases such as infectious diarrhea (i.e. Salmonella enterocolitis), pneumonia, intestinal compromise from colic (i.e. colon torsion), grain overload, and retained placenta/acute uterine infection post foaling. Although we have discovered some of the central laminar events occurring in SRL (including the same initial inflammation as occurs in organ injury and failure in human sepsis patients), we still have not established the events or signaling that result in laminar failure.

After many decades of frustration with failures of multiple therapies, we now have one therapy, continuous digital hypothermia (CDH), which has proven effective in the laboratory and clinical setting in many horses. We will use advanced biochemistry techniques, combined with two cutting edge research tools including kinome arrays and metabolomics analysis. The results will provide targets for pharmaceutical therapies to either replace or augment CDH, and will also for the first time determine effects of CDH in the normal digit (important to know for any commonly used therapy).

Advancing laminitis therapy will allow more at-risk animals to avoid the crippling consequences of SRL and return to their previous level of function in the equine industry as was witnessed with Paynter.

Laminitis causes failure of digital suspension, resulting in excruciating pain and often resulting in humane destruction of the horse. Our previous studies, using archived samples from two experimental models of laminitis, detected molecular changes that are helping us understand the steps preceding full-blown laminitis.

The goal of the proposed study is to identify at least three serum markers that would be useful for diagnosing the early, inapparent or “developmental” phase of laminitis and to detect the resulting tissue damage and the body’s immune response to that damage.

Based on our earlier studies, we will investigate blood levels of specific proteins using samples from horses without laminitis, horses in the early stage of the disease prior to lameness, and horses with overt laminitis. The studies will involve methods for the identification and quantification of proteins in tissue and blood samples and for the detection of specific classes of antibodies involved in the immune response.

Positive results from this study will then be used to develop diagnostic tests to detect incipient laminitis in horses that are believed to be at risk of developing the disease, such as horses with a prior history of laminitis, severe orthopedic injuries, colic, obesity, or horses that have ingested excess grain, and to assess lamellar tissue damage. New technology that allows the “multiplexing” of assays for several markers into a single assay will be used to generate an assay for lamellar tissue damage.

Lameness Research

Evidence indicates that race surfaces affect the likelihood for injuries in racehorses. Race surface design has the potential to significantly reduce injuries because race surfaces affect all racehorses training and racing on a surface. Therefore, race surface design is an attractive factor to manage to reduce racehorse injuries.

Mild and severe injuries to the fetlock are very common. Catastrophic injuries to the fetlock are the greatest cause of death in racehorses, causing about 50% of injury related deaths. Fetlock injuries are due to circumstances that cause the fetlock to extend beyond its normal range of motion (hyperextension).

We hypothesize that fetlock hyperextension, and thus related injuries, can be prevented by developing race surfaces that change the way the limb interacts with the surface. Our objective is to determine the characteristics that a race surface should have to prevent fetlock injuries.

It is not economically practical to build the number of race surfaces needed to determine the ideal surface for injury prevention. Thus, a computer modeling and simulation approach is being used because it is a powerful and economical tool for investigation of race surface characteristics on fetlock motion, and thus risk for injury. This approach can be used to assess the effect of surfaces presently installed, as well as those surfaces that do not presently exist. Racehorse fetlock motion will be predicted for a large number of surfaces with different characteristics.

Because the predictions are only as good as the computer model, the model will be evaluated for accuracy (validated) by comparing predictions with actual race surface behavior and racehorse fetlock motion that we previously measured simultaneously at two racetracks, one with a dirt surface and one with a synthetic surface. After validation, the model will be used to determine race surface characteristics that prevent fetlock hyperextension.

Osteoarthritis is the most common musculoskeletal problem in horses and leads to lameness, decreased athleticism, and early retirement. Unfortunately, routine diagnostic methods (radiographs, ultrasound, MRI, CT) all have shortcomings in evaluating articular cartilage, although MRI is currently the preferred imaging method. However, when contrast agents are injected into the joint prior to CT imaging (CCECT), they have the potential to provide far more information about the health of cartilage. In preliminary experiments we have demonstrated that the amount of CCECT contrast in the cartilage is strongly related to the amount of GAG content within articular cartilage in normal joints.

Our hypothesis is that CCECT is a safe and useful method to improve early diagnosis of joint disease. We will test this hypothesis by determining GAG concentrations in normal and diseased articular cartilage and comparing those amounts to CCECT attenuation. We will also test the safety of the contracts agent by evaluating articular cartilage samples for toxicity and lastly, compare the CCECT imaging modality to MRI. It is anticipated that in these experiments we will be able to demonstrate that decreasing GAG content is measurable using contrast CT studies allowing for the early detection of cartilage injury using readily available equipment.

The completion of this project will allow for the critical evaluation of CCECT as a method for the detection of early osteoarthritis in horses and will allow for applications of its use in clinical patients. If this method proves to be effective, it can be a useful tool for monitoring future treatment protocols in horses as well as future cartilage research as it offers a way of ante-mortem in depth evaluation of cartilage health.

The superficial digital flexor tendon (SDFT) is a commonly injured soft tissue structure in performance horses. Injury of this structure is site–specific and commonly affects the mid–portion of the SDFT. Prognosis for return to full athletic function is guarded due to the fact that often horses are placed back into work to soon and re–injury of the tendon occurs.

Therefore, it is important to be able to assess quantitatively the mechanical properties of tendons under load before the horse returns to full athletic use.

At the University of Wisconsin a novel technique called “Acoustoelastography (AEG) was developed, which interrelates the ultrasound wave propagation to the local tissue biomechanical stiffness. Pathological diseased tendon has less stiffness than normal healthy tendon. AEG can assess this in real–time without knowing/recording tissue loads or performing extensive numerical analysis on images.

The goals of this project are: To determine whether Acoustoelastography (AEG) can measure mechanical properties and strains non–invasively in abnormal equine tendons and secondly evaluate the healing of the equine superficial digital flexor tendon (SDFT) during recovery from tendon injury. In this study, we will evaluate tendon stiffness in the SDFT that had an injury and therefore pathologic changes. This stiffness will be compared to the normal stiffness of a SDFT.

We will then demonstrate secondly that the stiffness of a tendon changes during its healing process. Horses with injury to their SDFT will be followed for 6–12 months to show that stiffness increases as the tendon heals. We expect that this study will show that a simple non–invasive evaluation of tendon function is possible and is able to detect, monitor and help in the rehabilitation of tendon injury.

Storm Cat Career Development Award

The Storm Cat Career Development Award, inaugurated in 2006, is a $15,000 grant designed as an early boost to an individual considering a career in equine research. It has been underwritten annually by Mrs. Lucy Young Hamilton, a Grayson-Jockey Club Research Foundation board member whose family stood the retired champion stallion Storm Cat at Overbrook Farm.This year, two out of three award winners are for work in lameness research. They are:Bradley B. Nelson, Colorado State University Contrast CT for Cartilage Injury in Impact OA ModelHeidi Reesink, Cornell UniversityLubricin as a biotherapeutic for equine joint disease Information provided in this article was abbreviated from full descriptions of the projects and Storm Cat Awards provided by and available through the Grayson-Jockey Club Research Foundation.

The foundation also announced today that its board approved the appointment of Dr. Steve Reed, a prominent veterinarian affiliated with Rood & Riddle Equine Hospital in Lexington, Kentucky, to succeed Dr. Paul Lunn as chairman of the Research Advisory Committee.

Photos used in this article are from the archives of Hoofcare Publishing or are linked from the researchers' employing university web sites. Photo of James Belknap courtesy of Richard Booth.

Disclosure of Material Connection: The Hoof Blog (Hoofcare Publishing) has not received any direct compensation for writing this post. Hoofcare Publishing has no material connection to the brands, products, or services mentioned, other than products and services of Hoofcare Publishing. I am disclosing this in accordance with the Federal Trade Commission’s 16 CFR, Part 255: Guides Concerning the Use of Endorsements and Testimonials in Advertising.

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